RESPIRATORY DISEASES

ABEDULRAHMAN SHARIF, MD

Assistant Prof. of Neonatology

Department of Pediatrics
The Hashemite University
Introduction
• Respiratory disorders are the most frequent cause of
admission in term and preterm.

• It is occasionally difficult to distinguish respiratory from

non-respiratory etiologies on the basis of clinical signs
alone.

• Timely and appropriate therapy is essential to improve

outcome.

• Signs and symptoms of respiratory distress include

cyanosis, grunting, nasal flaring, retractions and
tachypnea.
Introduction
• Apnea: No respiratory effort for greater than 20 seconds or if
cessation of breathing lasts for more than 10 seconds and is
accompanied by bradycardia and or desaturation.

• Periodic breathing pattern, which shifts from a regular

rhythmicity to cyclic brief episodes of intermittent apnea, is
more common in preterm infants, who may have apneic
pauses of 5-10 sec followed by a burst of rapid
respirations at a rate of 50-60 breaths/min for 10-15 sec.

• Periodic breathing, a normal characteristic of neonatal

respiration, has no prognostic significance.
Respiratory Distress Syndrome
(Hyaline Membrane Disease)
INCIDENCE
• Respiratory distress syndrome occurs primarily in
premature infants; its incidence is inversely
related to gestational age and birth weight.

• It occurs in
• 60-80% of infants <28 wk of gestational age,
• 15-30% of those between 32 and 36 wk of gestational age,
• rarely in those >37 wk of gestational age.
INCIDENCE
The risk for development of
RDS increases with
1. Maternal diabetes,
2. Multiple births,
3. Cesarean delivery,
4. Precipitous delivery,
5. Asphyxia or hypoxemia
6. Cold stress or hypothermia
7. Hypovolemia and
hypotension
8. Maternal history of
previously affected infants.
The risk of RDS is
reduced in
1. Pregnancies with chronic
or pregnancy-associated
hypertension,
2. Maternal heroin use,
3. Prolonged rupture of
membranes,
4. Antenatal corticosteroid
prophylaxis
ETIOLOGY AND PATHOPHYSIOLOGY
• Surfactant deficiency (decreased production and secretion; increased
consumption) is the primary cause of RDS.

• Synthesis of surfactant depends on

1. normal pH,
2. temperature,
3. perfusion.

• Although rare, genetic disorders of mutations in protein part of the

surfactant may contribute to respiratory distress.

• The major constituents of surfactant are dipalmitoyl

phosphatidylcholine (lecithin), phosphatidylglycerol, apoproteins
(surfactant proteins SP-A, SP-B, SP-C, and SP-D), and cholesterol.
• Composition:
• 90% lipids
• 10% proteins
• With advancing gestational age,
increasing amounts of
phospholipids are synthesized in
type II alveolar cells.

• Surfactant is present in high

concentrations in fetal lung
homogenates by 20 wk of
gestation, but it does not reach the
surface of the lungs until later.

• It appears in amniotic fluid

between 28 and 32 wk of
gestation.

• Mature levels of pulmonary

surfactant are present usually
after 35 wk of gestation.

•Normal
Lecithin : Sphingomyeline ratio is
>=2 which indicates mature lungs.
• Function of lung surfactant
1. Decreases surface tension during expiration
2. Allows the alveolus to remain partly expanded
3. Maintains functional residual capacity
ETIOLOGY AND PATHOPHYSIOLOGY
• Alveolar atelectasis, hyaline membrane formation, and interstitial edema make the
lungs less compliant in RDS, so greater pressure is required to expand the
alveoli and small airways due to increased surface tension.

• Thus, at end-expiration, the volume of the thorax and lungs tends to approach
residual volume, and atelectasis may develop. Results in perfused but not
ventilated alveoli, causing hypoxia.

• Decreased lung compliance, small tidal volumes, increased physiologic dead

space, and insufficient alveolar ventilation eventually result in hypercapnia.

• The combination of hypercapnia, hypoxia, and acidosis produces pulmonary

arterial vasoconstriction with increased right-to left shunting through the
foramen ovale and ductus arteriosus and within the lung itself.

• Progressive injury to epithelial and endothelial cells from atelectasis

(atelectrauma), volutrauma, ischemic injury, and oxygen toxicity results in effusion
of proteinaceous material into the alveolar spaces.>> Bronchopulmonary
dysplasia
CLINICAL MANIFESTATIONS
• Signs of RDS usually appear within minutes to hours of birth.

• History of resuscitation at birth because of asphyxia or initial severe

respiratory distress (especially with a ELBW).

• Characteristically, tachypnea, grunting, intercostal and subcostal

retractions, nasal flaring, and cyanosis are noted.

• Breath sounds may be normal or diminished with a harsh tubular quality,

and inspiratory fine crackles may be heard.

• In most cases, the peak within 3 days, after which improvement is gradual.

• Improvement is often heralded by spontaneous diuresis and improved

blood gas at lower inspired oxygen levels and/or lower ventilator
support.
CLINICAL MANIFESTATIONS
• The course of untreated RDS is characterized by

1. Worsening of cyanosis, dyspnea and blood pressure.

2. Apnea and irregular respirations.

3. mixed respiratory-metabolic acidosis, edema, ileus, and oliguria.

4. Respiratory failure may occur in infants.

5. finally death can result from severe impairment of gas exchange, alveolar air
leaks (interstitial emphysema, pneumothorax), pulmonary hemorrhage, or
IVH.

• BPD is a form of chronic lung disease that often develops in

infants with severe RDS.
DIAGNOSIS
• The clinical course, chest x-ray findings, and blood gas and acid–
base values help establish the clinical diagnosis.

• On chest x-ray, the lungs may have a characteristic but not

pathognomonic appearance that includes a
1. fine reticular granularity of the parenchyma (Ground glass
appearance)
2. air bronchograms: Prominent air bronchograms represent
aerated bronchioles superimposed on a background of collapsed
alveoli.
3. Small lung volume
DIAGNOSIS
• Laboratory findings are characterized
1. initially by hypoxemia that may progress,
2. hypercapnia with respiratory acidosis
3. then variable metabolic acidosis.

• Echocardiography to rule out cyanotic congenital heart

disease as well as ascertain patency of the ductus
arteriosus and assess pulmonary vascular resistance
(PVR).
DIAGNOSIS
• Differential diagnoses are
1. GBS pneumonia
2. TTN,
3. Persistent pulmonary hypertension,
4. aspiration (meconium, amniotic fluid) syndromes,
5. spontaneous pneumothorax,
6. pleural effusions,
7. congenital anomalies.

• Transient tachypnea (TTN) may be distinguished by its shorter and

milder clinical course and is characterized by low or no need for oxygen
supplementation.

• In the differential diagnosis, early-onset sepsis may be indistinguishable

from RDS.
• In neonates with GBS pneumonia, the chest radiograph may be identical to that for
RDS. So septic workup should be done.
PREVENTION
v Avoidance of unnecessary or early cesarean section (<39 wk) or induction of
labor.

v Administration of antenatal corticosteroids to women before 34 wk of

gestation significantly reduces the incidence and mortality of RDS as well as
1. overall mortality,
2. the need for and duration of ventilatory support and admission to a neonatal ICU,
3. the incidence of severe IVH, necrotizing enterocolitis, and neurodevelopmental
impairment.

• Steroids are recommended for all women in preterm labor who are likely to
deliver within 1 wk and are safe with no adverse effects.
• Betamethasone better than dexamethasone.

v CPAP started at birth is as effective as prophylactic or early surfactant and is the

approach of choice for the delivery room management of a preterm neonate at risk
for RDS.
TREATMENT
• Therapy requires careful and frequent monitoring of
1. Heart and respiratory rates
2. Oxygen saturation
3. Pao2, Paco2, pH and serum bicarbonate
4. Electrolytes
5. Glucose
6. Hematocrit
7. Blood pressure and perfusion
8. Kidney function tests
9. Temperature
TREATMENT
• Avoid hypothermia and minimize oxygen consumption, the infant
should be placed in an incubator or radiant warmer, to keep core
temperature between 36.5 and 37°C.

• Calories and fluids should initially be provided intravenously with

D10%W and amino acids.
• Excessive fluids (>140 mL/kg/ day) contribute to the development
of patent ductus arteriosus (PDA) and BPD.

• Because of the difficulty of distinguishing other bacterial infections

from RDS, empirical antibiotic therapy is indicated until the
results of blood cultures are available.
• Ampicillin with an aminoglycoside is suggested.
TREATMENT
vOxygen therapy:
• Warm humidified oxygen should be provided at a concentration initially
sufficient to keep saturation 88-94% in order to maintain normal tissue
oxygenation while minimizing the risk of oxygen toxicity.

• If oxygen saturation cannot be kept >90% at inspired oxygen concentrations

of 40-70% or greater, applying CPAP.

• Another approach is to INtubate the preterm infant, administer intratracheal

SURfactant and then Extubate the infant and begin CPAP - INSURE.

• Early nasal CPAP is beneficial as compared to intubation and

prophylactic surfactant, including lower mortality or BPD with CPAP
treatment.
TREATMENT
vOxygen therapy:
• If an infant with RDS undergoing CPAP cannot keep oxygen saturation >90%
while breathing 40-70% oxygen, Infants with respiratory failure or persistent
apnea assisted mechanical ventilation and surfactant are indicated.

• Reasonable measures of respiratory failure are:

1. arterial blood pH <7.20,
2. arterial blood Pco2 of 60 mm Hg or higher,
3. oxygen saturation <90% at oxygen concentrations of 40-70% and CPAP of
5-10 cm H2O.

• Permissive hypercapnia in which priority is given to the prevention or

limitation of lung injury from the ventilator by tolerating relatively high levels of
Paco2 rather than maintenance of normal blood gas values.
TREATMENT
v Surfactant:
• Immediate effects of endotracheal surfactant replacement therapy include
1. improved oxygenation,
2. reduced ventilatory support,
3. increased pulmonary compliance,
4. improved chest radiograph appearance.

• Repeated dosing is given every 6-12 hr for a total of 2 to 4 doses, depending on the
preparation.

• Complications of surfactant therapy include

1. transient hypoxia,
2. hypercapnia,
3. bradycardia and hypotension,
4. blockage of the endotracheal tube,
5. pulmonary hemorrhage.
COMPLICATIONS OF RESPIRATORY DISTRESS
SYNDROME AND INTENSIVE CARE
A. Complications of tracheal intubation.

B. Risks associated with umbilical arterial and venous

catheterization.
• Renovascular hypertension may occur days to weeks after
umbilical arterial catheterization in a small proportion of
neonates.

C. Air leaks are a common complication of the management of

infants with RDS.
COMPLICATIONS OF RESPIRATORY DISTRESS
SYNDROME AND INTENSIVE CARE
D. Some neonates with RDS may have clinically
significant shunting through a PDA diagnosed
by echocardiography.

• Manifestations of PDA may include

1. a hyperdynamic precordium, bounding
peripheral pulses, wide pulse pressure, and
a continuous (machinery) or systolic murmur
with or without extension into diastole;
2. radiographic evidence of cardiomegaly and
increased pulmonary vascular markings;
3. hepatomegaly;
4. increasing oxygen dependence;
5. carbon dioxide retention.
COMPLICATIONS OF RESPIRATORY DISTRESS
SYNDROME AND INTENSIVE CARE
E. Bronchopulmonary dysplasia (BPD) :

• BPD was defined as persistent oxygen dependency up to 28 days

of life.

• The severity of BPD-related pulmonary dysfunction and

neurodevelopmental impairment in early childhood is more accurately
predicted by an oxygen dependence at 36 weeks’ postmenstrual
age (PMA) in infants <32 weeks’ gestational age (GA) and at 56
days of age in infants with older GA.

• The occurrence of BPD is inversely related to gestational age.

COMPLICATIONS OF RESPIRATORY DISTRESS
SYNDROME AND INTENSIVE CARE
v Bronchopulmonary dysplasia (BPD) :
• Diagnosis:

• Instead of showing improvement on the 3rd or 4th day, which would

be consistent with the natural course of RDS, some infants
demonstrate an increased need for oxygen and ventilatory
support.

• The chest radiograph may reveal pulmonary interstitial

emphysema, wandering atelectasis with concomitant hyperinflation,
and cyst formation (chronic lung changes).
COMPLICATIONS OF RESPIRATORY DISTRESS
SYNDROME AND INTENSIVE CARE
v Bronchopulmonary dysplasia (BPD) :
• Treatment of BPD includes nutritional support, fluid restriction, drug
therapy, maintenance of adequate O2, and prompt treatment of
infection.

• Vitamin A supplementation in VLBW infants reduces the risk of

BPD.

• Early use of nasal CPAP and rapid extubation with transition to

nasal CPAP are associated with a decreased risk of BPD.

• Nutritional supplementation.

• Diuretic therapy(Furosemide).
COMPLICATIONS OF RESPIRATORY DISTRESS
SYNDROME AND INTENSIVE CARE
v Bronchopulmonary dysplasia (BPD) :

• Inhaled bronchodilators (beta-2 agonist) and Ipratropium

bromide improve lung mechanics by decreasing airway resistance.

• Methylxanthines (theophylline and Caffeine) are used in infants with

BPD to increase respiratory drive, decrease apnea, improve
diaphragmatic contractility, decrease PVR and increase lung
compliance.

• Preventive therapy of BPD with postnatal dexamethasone may

reduce the time to extubation and may decrease the risk of BPD but
is associated with substantial short- and long-term risks.
PROGNOSIS
• Antenatal steroids, postnatal surfactant use, and
improved modes of ventilation have resulted in low
mortality from RDS (≈10%).

• Mortality increases with decreasing gestational age.

• Although 85-90% of all infants surviving RDS after

requiring ventilatory support are normal, the outlook is
much better for those weighing >1,500 g.

• Survivors with BPD often go home on a regimen of

oxygen, diuretics, and bronchodilator therapy.
PROGNOSIS
• Cardiac complications of BPD include pulmonary
hypertension, cor pulmonale, systemic hypertension and
left ventricular hypertrophy.

• Infants are at risk for severe respiratory syncytial virus

infections and must receive prophylactic therapy.

• Noncardiorespiratory complications of BPD include

growth failure, psychomotor retardation, and parental
stress, as well as sequelae of therapy.
Transient Tachypnea of the Newborn
Transient Tachypnea of the Newborn
• Normally after delivery, Air entry into the lungs displaces
fluid. The remaining fluid is removed via the pulmonary
lymphatics, upper airway, mediastinum, and pleural space.

• The syndrome is believed to be secondary to slow absorption

of fetal lung fluid, resulting in decreased pulmonary
compliance and tidal volume and increased dead space.

• In severe cases, retained fetal lung fluid may interfere with the
normal postnatal fall in PVR, resulting in persistent
pulmonary hypertension; a mild surfactant deficiency may be
present.
Transient Tachypnea of the Newborn
• Transient tachypnea is frequently a diagnosis of
exclusion.

• The distinctive features of transient tachypnea are

1. rapid recovery of the infant
2. the absence of radiographic findings for RDS and other
lung disorders.
3. Occur in term and late term infants.
Risk factors
Transient Tachypnea of the Newborn
• Transient tachypnea is most common after term
cesarean delivery.

• It is characterized by the early onset of tachypnea,

sometimes with retractions, or expiratory grunting and,
occasionally, cyanosis that is relieved by minimal oxygen
supplementation (<40%).

• Most infants recover rapidly, usually within 3 days.

• Hypercapnia and acidosis are uncommon.

TTN
• The chest generally
sounds clear without
crackles or wheeze, and
the chest radiograph
shows
1. prominent pulmonary
vascular markings,
2. fluid in the intralobar
fissures,
3. overaeration, flat
diaphragms,
4. rarely, small pleural
effusions.
Transient Tachypnea of the Newborn
• Treatment
• Supportive.

• Antibiotics started when baby need O2 support more

than 6 hours due to difficulty to differentiate from
sepsis.

• The term “malignant transient tachypnea of the

newborn” has been used to describe the refractory
hypoxemia as a result of pulmonary hypertension and
require ECMO support.
• The initial approach to these infants is similar to that of RDS plus
the concern for pulmonary hypertension.
Meconium Aspiration
Meconium Aspiration
• Meconium-stained amniotic fluid is found in 10-15% of births
and usually occurs in late-term, term or post-term infants.

• Meconium aspiration syndrome (MAS) develops in 5% of such

infants; 30% require mechanical ventilation and 3-5% die.

• Usually, but not invariably, fetal distress and hypoxia occur

before the passage of meconium into amniotic fluid.

• The infants are meconium stained and may be depressed

and require resuscitation at birth (low APGAR score).

• Infants with MAS are at increased risk of persistent pulmonary

hypertension.
CLINICAL MANIFESTATIONS
• Respiratory distress within the first hours, with
tachypnea, retractions, grunting, and cyanosis observed
in severely affected infants.

• Partial obstruction of some airways may lead to

pneumomediastinum, pneumothorax, or both.
Overdistention of the chest may be prominent.

• The condition usually improves within 72 hr, but when its

course requires assisted ventilation, it may be severe
with a high risk for mortality.
Diagnosis
• The typical chest radiograph
is characterized by
1. patchy infiltrates,
2. coarse streaking of both
lung fields,
3. increased
anteroposterior
diameter,
4. flattening of the
diaphragm.
PREVENTION
• The risk of meconium aspiration may be decreased by
rapid identification of fetal distress and initiation of
prompt delivery in the presence of late fetal heart rate
deceleration or poor beat-to-beat fetal heart rate
variability.

• Amnioinfusion, it does not reduce the risk of MAS,

cesarean delivery, or other major indicators of maternal or
neonatal morbidity.

• Intrapartum nasopharyngeal suctioning in infants

with meconium-stained amniotic fluid does not
reduce the risk for MAS.
European Resuscitation Council
Guidelines 2021
TREATMENT
• Routine intubation to aspirate the lungs of vigorous and non-
vigorous infants born through meconium-stained fluid is not
effective in reducing the MAS or other major adverse outcomes.

• Treatment of the MAS includes supportive management for

respiratory distress.

• Administration of surfactant and/or iNO to infants with MAS and

hypoxemic respiratory failure, or pulmonary hypertension.

• ECMO.
PROGNOSIS
• The mortality rate of meconium-stained infants is considerably
higher than that of non-stained infants.

• The decline in neonatal deaths caused by MAS during the last

decades is related to improvements in obstetric and neonatal
care.

• Residual lung problems are rare, but include symptomatic

cough, wheezing, and persistent hyperinflation for up to 5-10
yr.

• The ultimate prognosis depends on the extent of CNS injury

from asphyxia and the presence of associated problems such
as pulmonary hypertension.
 Extrapulmonary Air
Leaks (Pneumothorax,
Pneumomediastinum, Pulmonary
Interstitial Emphysema,
Pneumopericardium)